SEPTRA GRAPE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SEPTRA GRAPE (SEPTRA GRAPE).
Septra Grape (trimethoprim/sulfamethoxazole) inhibits bacterial folic acid synthesis via sequential blockade: sulfamethoxazole inhibits dihydropteroate synthase, and trimethoprim inhibits dihydrofolate reductase, leading to bactericidal activity.
| Metabolism | Sulfamethoxazole is metabolized via N-acetylation and glucuronidation; trimethoprim is metabolized to oxide and hydroxylated metabolites. Both are primarily excreted renally. |
| Excretion | Renal: 50-70% unchanged (trimethoprim), 30-50% as N-acetyl metabolite; sulfamethoxazole: 70-80% as metabolites, 20-30% unchanged; biliary excretion minimal (<5% total). |
| Half-life | Trimethoprim: 8-10 hours (renal impairment >24h). Sulfamethoxazole: 10-13 hours (acetylation phenotype; prolonged in renal impairment). Clinical: Dosing interval generally 12h; adjust CrCl <30 mL/min. |
| Protein binding | Trimethoprim: 42-46% (primarily albumin). Sulfamethoxazole: 68-72% (albumin; decreased in uremia). |
| Volume of Distribution | Trimethoprim: 1.3-1.8 L/kg (widespread; high tissue penetration, including CNS). Sulfamethoxazole: 0.15-0.3 L/kg (predominantly extracellular). |
| Bioavailability | Oral: Trimethoprim 95-100%, sulfamethoxazole 85-95% (both well absorbed). IV: 100%. |
| Onset of Action | Oral: 1-4 hours (therapeutic levels achieved in 2-4h). IV: 1-2 hours (time to bactericidal concentrations). |
| Duration of Action | 12-24 hours; bacteriostatic activity persists ~12h due to dual folate inhibition. Clinical: Twice-daily dosing for most infections. |
160 mg trimethoprim / 800 mg sulfamethoxazole (1 double-strength tablet) orally every 12 hours.
| Dosage form | SUSPENSION |
| Renal impairment | CrCl 30-50 mL/min: reduce dose by 50% or extend interval to 24 hours. CrCl <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class B: reduce dose by 50% and monitor liver function. Child-Pugh Class C: contraindicated. |
| Pediatric use | 8 mg/kg/day trimethoprim / 40 mg/kg/day sulfamethoxazole in two divided doses orally every 12 hours. |
| Geriatric use | Use lower end of dosing range due to increased risk of adverse effects; monitor renal function and electrolytes; adjust dose if CrCl <50 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SEPTRA GRAPE (SEPTRA GRAPE).
| Breastfeeding | Trimethoprim and sulfamethoxazole are excreted into breast milk; M/P ratio for sulfamethoxazole approximately 0.07-0.32, trimethoprim approximately 0.4-0.7. Theoretical risk of kernicterus in premature or hyperbilirubinemic infants. Use with caution; avoid in nursing infants with G6PD deficiency. Generally considered compatible if infant is healthy. |
| Teratogenic Risk | First trimester: Exposure associated with increased risk of neural tube defects (1.9-3.4% vs 0.5% baseline), cardiovascular malformations, and oral clefts due to folate antagonism. Second/third trimesters: Risk of kernicterus in neonates from sulfonamide displacement of bilirubin from albumin; avoid near term. Also associated with growth restriction and low birth weight. |
■ FDA Black Box Warning
Fatal hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias have been reported.
| Serious Effects |
Hypersensitivity to sulfonamides, trimethoprim, or any component; megaloblastic anemia due to folate deficiency; severe hepatic impairment; marked renal impairment (CrCl <15 mL/min) unless used for PCP; concomitant dofetilide (increased risk of cardiac arrhythmias).
| Precautions | Monitor for severe hypersensitivity reactions, hematologic toxicity (especially with folate deficiency), hemolysis in G6PD deficiency, hepatotoxicity, electrolyte disturbances (hyperkalemia with high-dose trimethoprim), and Clostridioides difficile-associated diarrhea. |
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| Fetal Monitoring | Maternal: CBC with differential and platelets, renal function tests, liver function tests, serum folate levels if prolonged therapy. Fetal: Detailed anatomy ultrasound at 18-20 weeks to assess for neural tube defects; consider fetal echocardiography if first-trimester exposure. Monitor neonatal bilirubin levels if maternal use near term. |
| Fertility Effects | Trimethoprim may impair spermatogenesis in males via antifolate effects; reversible upon discontinuation. No known effect on female fertility. In women, folate depletion could theoretically affect ovulation or implantation, but clinical data limited. |